Blindness can occur when any part of the vision system (the optics, the retina, the optic nerve or the visual cortex) are interrupted or destroyed. The leading cause of blindness in the developed world is Retinal Degeneration (RD). The two principle diseases resulting in RD are Age Related Macular Degeneration (AMD) and Retinitis Pigmentosa (RP). AMD is the leading cause of blindness in the developed world. According to a March 1997 review in the Optometry Journal, 10 percent of the U.S. population over the age of 52 has AMD and 33 percent of individuals over the age of 75 have AMD.
AMD can be categorized into two forms, a non-neovascular (dry, atrophic) form and a neovascular (wet, exudative) form. The non-neovascular form involves alterations of pigment distribution, loss of retinal pigment epithelium (RPE) cells and photoreceptors, and diminished retinal function due to an overall atrophy of the cells. The neovascular form of AMD involves proliferation of abnormal choroidal vessels, which penetrate the Bruch's membrane and RPE layer into the subretinal space forming extensive clots and scars. The cause of AMD is unknown.
RP is a name given to a large group of degenerative diseases. The dominant form of RP is associated with mutations in the visual pigment, rhodopsin protein. These mutations account for about 25 percent of RP cases in the U.S.
Normal retinal cell function is a photo-induced electrochemical reaction converting light energy into an electrical impulse. The photochemical reaction begins with the absorption of light by Rhodopsin. Rhodopsin breaks down into several intermediate compounds, but eventually forms metarhodopsin II (activated rhodopsin). This chemical causes electrical impulses that are transmitted via synapses to the first complex array of interneurons (bipolar cells and horizontal cells). These in turn connect to the ganglion cells, whose axons form the optic nerve.
The same electrical impulse travels to the visual cortex of the brain via the optic nerve and results in a vision sensation. With AMD, RP and other Retinal Degenerative (RD) diseases, photoreceptor retinal cells atrophy and eventually lose cell function. Since the bipolar and horizontal cells no longer receive neuronal signals, the retinal interneuronal layers undergo remodeling or arborization. The neural network is “pruned” and refined by mechanisms that include cell death, selective growth, loss of neurites and elimination of synapses (Neely and Nicholls, 1995). This natural phenomenon is related to the adage: “use it or lose it.”
It has been demonstrated that electrical stimulation of ganglion cells shows a rescue or neurotrophic effect, which promotes cell survival. Specifically, several studies performed on spiral ganglion cells show a survival due to electrical stimulation from cochlear implants (Leake et al., 1991; Leake et al., 1999). Recently documented studies of implanted human subjects with Microphotodiode Arrays (MPDA) have shown an overall improvement in vision. The results indicate that the MPDA in effect has not restored vision in the specific area in which the implant is placed; instead, results indicate a neurotrophic rescue effect due to the electrical stimulation on the remaining retinal cells.
The application of electrical stimulation to organ systems other than the ocular system is known to promote and maintain certain cellular functions. Electrical stimulation has been documented in bone growth and spinal cord growth, as well as in cochlear cell survival as mentioned earlier (Dooley et al., 1978; Evans et al., 2001; Kane, 1988; Koyama et al., 1997; Lagey et al., 1986; Politis and Zanakis, 1988a; Politis and Zanakis, 1988b; Politis and Zanakis, 1989; Politis et al., 1988a; Politis et al., 1988b). Electrical stimulation has also been applied in Deep Brain Stimulators for Parkinson's Disease and Essential Tremor. This electrical stimulation temporarily disables the overactive cells that cause Parkinson's disease symptoms (O'Suilleabhain P. E., 2003).
Electrical stimulation of the ocular system has been under study for several decades. As early as the 1890's, scientists have been experimenting with the use of an electric current to produce an artificial vision sensation or phosphene. Brindley's work in the 1950's documents the thresholds needed to induce such a phosphene (Brindley 1955). There are also numerous amounts of animal work that suggest that the retina responds to externally applied electrical stimulation (Kuras, A. V., Khusainovene N P. 1981, Knighton, R. W. 1975, Humayun, M. S. 2001, Grumet, A. E. et. al. 2001).
Tassicker described the notion of an implanted artificial vision device in a U.S. patent in 1956 (U.S. Pat. No. 2,760,483). A light-sensitive selenium cell was placed behind the retina of a blind patient and transiently restored the patient's ability to perceive a sensation of light. Since then, several groups have been working to develop a device that can be implanted in place of the degrading photoreceptors. These groups attempt to restore vision by using photonic properties of semiconductors designed to mimic the electric charge that damaged retinal cells would otherwise generate. However, there are few devices or treatments available that can slow, stop or reverse retinal degeneration.
Recent studies of the electrical stimulation of the cut optic nerve show a survival of axotomized retinal ganglion cells in vivo. The conclusion from this experimentation demonstrates that electrical stimulation of the optical nerve enhances the survival of axotomized retinal ganglion cells in vivo due to electrical activation of their soma (Morimoto T., 2002).
These findings led me to find a means for providing electrical stimulation to a diseased eye in a minimally invasive manner, to stimulate the regrowth, rescue and survival of ocular neural tissue and the entire ocular system for the treatment of blinding diseases such as Retinitis Pigmentosa, Age Related Macular Degeneration, and other Retinal Degenerative diseases.